Role of Pulsatile Insulin Secretion.

描述（由申请人提供）：2型糖尿病正在增加， 以惊人的速度蔓延。这种疾病的根本原因仍然是 不知道。TTDM患者存在胰岛素抵抗和胰岛素缺陷 分泌物近30年来，人们已经知道胰岛素是在体内分泌的。 高频间歇脉冲然而，由于这些脉冲仅导致 在通常的血液取样部位中胰岛素浓度的小振荡， 他们很难学习。PI实验室与 弗吉尼亚大学的Johannes Veldhuis开发并验证了 现在可以可靠地量化人类胰岛素脉冲分泌的方法。 用这些方法进行的研究表明，几乎所有的胰岛素都是在体内分泌的。 这些间歇性脉冲每隔6分钟出现一次。我们还表明 实现胰岛素分泌的调节（例如餐后） 通过这些脉冲的放大。此外，肝脏通常暴露于 当这些脉冲被分泌到门静脉时， 流向肝脏的静脉以前的研究没有检查的重要性 这些物质对胰岛素的作用产生脉冲。 在目前的研究中，我们计划首先 确定患者进食后胰岛素分泌如何受到干扰 关于TTDM我们怀疑它会有缺陷，因为胰岛素的大小 脉冲大大减少。此外，我们怀疑这是因为 分泌胰岛素的细胞数量减少。我们将测试这一点， 在狗的模型中移除大约40%和70%的这些细胞 预期我们将产生TTDM中存在的相同缺陷。我们 也将确定肝脏暴露在这些环境中的重要性 高胰岛素浓度才能正常发挥作用。这很重要，因为 糖尿病患者必须用胰岛素治疗， 不同的方式。未来系统的设计者，以取代患者的胰岛素 (e.g.通过移植或设备）需要评估的重要性， 脉冲式胰岛素分泌胰岛素作用。

DESCRIPTION (Provided by applicant): Type-2 diabetes is increasing in prevalence at an alarming rate. The underlying cause of this disease is still not known. Patients with TTDM have insulin resistance and defective insulin secretion. It has been known for almost 30 years that insulin is secreted in high frequency intermittent pulses. However as these pulses result in only small oscillations in insulin concentration in the usual blood sampling sites, they have been hard to study. The laboratory of the PI in collaboration with Johannes Veldhuis at the University of Virginia have developed and validated methods that can now reliably quantify pulsatile insulin secretion in humans. Studies with these methods have revealed that almost all insulin is secreted in these intermittent pulses which occur at 6-minute intervals. We have also shown that the regulation of insulin secretion (for example after a meal) is achieved by the amplification of these pulses. Also, the liver is normally exposed to huge insulin concentration changes as these pulses are secreted into the portal vein that drains to the liver. No prior studies have examined the importance of these masses pulses on insulin action. In the present studies we plan to first establish how insulin secretion after meal ingestion is disturbed in patients with TTDM. We suspect that it will be deficient because the size of the insulin pulses is greatly decreased. Further, we suspect that this is because the number of cells that secrete insulin are decreased. We will test this by removing approximately 40 percent and 70 percent of these cells in a dog model with the expectation that we will create the same defect present in TTDM. We will also establish how important it is that the liver be exposed to these large insulin concentrations to function normally. This is important since patients with diabetes have to treat themselves with insulin in a very different manner. Designers of future systems to replace insulin in patients (e.g. by transplantation or devices) need to be appraised of the importance of pulsatile insulin secretion insulin action.